Antiviral Treatment of HCV-Infected Patients with B-Cell Non-Hodgkin Lymphoma: ANRS HC-13 Lympho-C Study

Laurent Alric (1, 2) , Caroline Besson (3, 4) , Nathanael Lapidus (5, 6) , Juliette Jeannel (1, 2) , Jean-Marie Michot (3, 4) , Patrice Cacoub (7, 8) , Danielle Canioni (9, 10) , Stanislas Pol (11, 10) , Frédéric Davi (7, 8) , Pascaline Rabiega (5, 6) , Loic Ysebaert (12) , Delphine Bonnet (1, 2) , Olivier Hermine (13, 10)

1 PHARMA-DEV - Pharmacochimie et Biologie pour le Développement
2 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
3 IMVA - U1184 - Immunologie des Maladies Virales et Autoimmunes
4 Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre]
5 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
6 CHU Saint-Antoine [AP-HP]
7 CHU Pitié-Salpêtrière [AP-HP]
8 UPMC - Université Pierre et Marie Curie - Paris 6
9 Service de pathologie [CHU Necker]
10 UPD5 - Université Paris Descartes - Paris 5
11 Service d'hépatologie médicale [CHU Cochin]
12 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
13 Service d'immuno-hématologie pédiatrique [CHU Necker]

Hepatitis C virus (HCV) infection is associated with lymphoproliferative disorders and B-cell non-Hodgkin lymphomas (B-NHLs). Evaluation of the efficacy and safety profiles of different antiviral therapies in HCV patients with B-NHL is warranted. Methods: First, we evaluated the sustained virologic response (SVR) and safety of Peg-interferon-alpha (Peg-IFN) + ribavirin +/- first protease inhibitors (PI1s) therapy in 61 HCV patients with B-NHL enrolled in a nationwide observational survey compared with 94 matched HCV-infected controls without B-NHL. In a second series, interferon-free regimens using a newly optimal combination therapy with direct-acting antiviral drugs (DAAs) were evaluated in 10 patients with HCV and B-NHL. Results: The main lymphoma type was diffuse large B-cell lymphoma (38%) followed by marginal zone lymphoma (31%). In the multivariate analysis, patients with B-NHL treated by Peg-IFN-based therapy exhibited a greater SVR rate compared with controls, 50.8% vs 30.8%, respectively, p<0.01, odds ratio (OR) = 11.2 [2.3, 52.8]. B-NHL response was better (p = 0.02) in patients with SVR (69%) than in patients without SVR (31%). Premature discontinuation of Peg-IFN-based therapy was significantly more frequent in the B-NHL group (19.6%) compared with the control group (6.3%), p<0.02. Overall, survival was significantly enhanced in the controls than in the B-NHL group (hazard ratio = 34.4 [3.9, 304.2], p< 0.01). Using DAAs, SVR was achieved in 9/10 patients (90%). DAAs were both well tolerated and markedly efficient. Conclusions: The virologic response of HCV-associated B-NHL is high. Our study provides a comprehensive evaluation of different strategies for the antiviral treatment of B-NHL associated with HCV infection.

Mots clés: Aged; Antiviral Agents / therapeutic use; Drug Therapy; Combination; Enzyme-Linked Immunosorbent Assay; Female; Genotype; Hepacivirus / genetics; Hepacivirus / isolation & purification; Hepatitis C / complications; Hepatitis C / drug therapy; Hepatitis C / mortality; Hepatitis C / virology; Humans; Interferon-alpha / therapeutic use; Lymphoma; B-Cell / complications; B-Cell / diagnosis; B-Cell Marginal Zone / complications; Large B-Cell Diffuse / complications; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Polyethylene Glycols / therapeutic use; Proportional Hazards Models; Protease Inhibitors / therapeutic use; RNA; Viral / blood; Viral / metabolism; Recombinant Proteins / therapeutic use; Ribavirin / therapeutic use; Survival Rate; Treatment Outcome

Domaines: Médecine humaine et pathologie

Laurent Alric, Caroline Besson, Nathanael Lapidus, Juliette Jeannel, Jean-Marie Michot, et al.. Antiviral Treatment of HCV-Infected Patients with B-Cell Non-Hodgkin Lymphoma: ANRS HC-13 Lympho-C Study. PLoS ONE, 2016, 11 (10), pp.e0162965. ⟨10.1371/journal.pone.0162965⟩. ⟨hal-01408993⟩